The cornea is the eye's outermost layer. It is a clear, dome-shaped surface that covers the front of the eye. The corneal structure is a highly organized group of cells and proteins. To see well, all layers of the cornea must be free of any cloudy or opaque areas.
Corneal tissue comprises five basic layers: the epithelial layer, Bowman's layer, the stroma, Decemet's membrane, and the endothelial layer. The cells of the endothelial layer play the most significant role in keeping the cornea clear. Under normal conditions, fluid travels slowly from the inside of the eye into the middle of the corneal layer (stroma). The endothelium's primary task is to pump this excess fluid out of the stroma. Without this pumping action, the stroma would swell with water, become hazy, and ultimately become opaque. Often due to pathology or an injury, endothelial cells may be destroyed. For all practical purposes, corneal endothelial cells do not reproduce. Thus, when endothelial cells are lost, either by trauma or disease, the lost cells are not replaced, and adjacent endothelial cells migrate and expand into the defect.
Corneal edema (swelling) occurs when the endothelial cell density is below a certain level, usually below about 400 cells/mm2. At birth, endothelial density varies between about 3,500 and 4,000 cells/mm2 (Kaufman et al. The Cornea; Second Edition on CD-Rom; Butterworth-Heinemann (1999)). As individuals age, there is a gradual attrition of corneal endothelial cells, so that when a normal individual reaches the age of 70 or older, the endothelial cell count may be only 2,500 cells/mm2. Clear vision depends on corneal clarity, which in turn depends on corneal deturgesence. Advanced corneal swelling is associated with severe vision loss and blindness. Corneal opacities due to disease or scarring are also associated with visual loss and, if severe, blindness.
Corneal transplantation is the only available therapy to remedy irreversible corneal edema or scarring. Corneal transplant therapy involves replacing the diseased, scarred or traumatized cornea with a healthy, clear cornea obtained from an organ donor. Corneal transplants are very common in the United States—it is reported that upwards of 50,000 are performed per year with a larger number being performed worldwide. Such procedures have a success rate of about 85%, making them the most successful type of surgical transplant procedures being performed.
As in other cases of organ transplantation, it is necessary to perform various tests on the donor's blood to rule out various infectious diseases that may be transmitted to the recipient, resulting in a delay in the surgical procedure being performed. Not infrequently, donor tissue must be transported, causing further delay. Therefore, it is necessary to undertake in vitro storage or maintenance of the harvested tissue and cells until transplantation occurs. With a donor cornea, the corneal tissue must be preserved in a way that the viability and density of the corneal cells, particularly those of the endothelial layer, are preserved, and that the cornea does not swell and maintains its clarity.
Various solutions and media have been developed to preserve tissues for storage and/or transportation for later use. However, even with specially prepared available storage media, the practical storage life is limited. For example, the widely used McCarey-Kaufman medium is considered to be useful in the preservation of corneal tissues for up to four days. The most commonly used medium in U.S. eyebanks for corneal preservation is the commercially available Optisol™ solution (Bausch & Lomb), designed for intermediate storage at 4° C. Optisol™ solution is a serum-free medium containing a base medium, a buffer, chondroiton sulfate, dextran (molecular weight 40K), vitamins, and ATP precursors. Although studies, (e.g., Kaufman et al. Arch Ophthalmol; 109:864-868 (1991); Lindstrom et al. Am Journal of Ophthalmol; 114:345-346 (1992)) have reported that Optisol™ is effective at preserving endothelial structure for up to two weeks, there is a significant loss of endothelial viability after this time and the majority of surgeons prefer not to use a cornea which has been stored for more than about five days in this medium. There is therefore a need in the art to develop an improved corneal storage medium that facilitates the preservation of corneal tissue over a longer period of time.